Tuesday, April 13, 2010

LKB1/AMPK Tumor Suppressor Pathway Controls Cell Growth and Metabolism

Also speaking yesterday at the biology-chemistry meeting at the New York Academy of Science was Dr. Reuben Shaw of the Salk Institute for Biological Studies. He showed his work which points to one tumor suppressor pathway's link to metabolism. This is very interesting work: metabolic genetic types or disease or even food may be linked to cancer. This would add to disease prevention and treatment. You can look up in a textbook or online what a tumor suppressor pathway is. There are several of them. As you probably know, tumor growth is a result of non-regulation of cell growth. Usually, apoptotic molecular cell reactions guide a cell to its programmed cell death. these reactions are triggered by chain of events down to DNA. Transcriptions factors and cofactors bind to DNA and regulate if a gene will be transcribed (copied) or not. Genes express amino acids which in turn make proteins which in turn, as enzymes or regular proteins, drive reactions. For instance, transcription factors determine whether the protein 53(p53) gene, which encodes the p53 protein, will be transcribed and how often. This is a tumor-suppressor protein, as other ones are. It regulates cell growth and apoptosis and conserves genetic stability by preventing genome mutation, which may lead to cancer.

Serine/threonine kinase 11(LKB1) is a protein kinase. It modifies other proteins by adding phosphate groups to them, rendering them active or inactive, largely because their three-dimensional structures is changed, allowing them to fit or not on cellular substrates. In the familial cancer Peutz-Jeghers Syndrome (PDS) and 30 percent of cases of non small cell lung cancer (NSCLC), this gene is mutated. Loss of its function in genetically-engineered mice leads to tumor formation or metabolic disease. Metformin, a generic drug widely used to treat diabetes, lowers blood glucose through the LKB1-AMPK pathway in the liver. Dr. Shaw is investigating the pathway to further understand the molecular basis behind these reactions. 5' adenosine monophosphate-activated protein kinase (AMPK) is involved in regulating glucose, cholesterol and lipid metabolism in specialized metabolic tissues, such as the liver, muscle and adipose tissue.

Dr. Shaw has found the protein kinase mammalian target of rapamycin (mTOR) to be involved. AMPK phosphorylates the substrate of mTOR, allowing for mTOR to be inhibited and apoptosis to happen, thus preventing cancer. These steps are also involved in the transcriptional control of glucose metabolism.

Look up Dr. Shaw on www.pubmed.gov!

Disclaimer: None of the above information can be taken as a substitute for advice from a medical professional such as a physician.

My third book, Pocket Guide to Fitness, is available on www.louizapatsis.com, http://www.authorhouse.com, www.bn.com and http://www.amazon.com. If you look up my name on those Web sites, you will find my other books The Boy in a Wheelchair and Life, Work and Play: Poems and Short Stories.

No comments: